Two novel quinazolines (2 and 3) related to both prazosin and its open analogue 1 were synthesized, and their biological profile at α1- adrenoceptor subtypes was assessed by functional assays in rat isolated tissues, namely prostatic vas deferens (α(1A)), spleen (α(1B)) and aorta (α(1D)). Furthermore, the binding profile of 3 was assessed at native α2 and D2 receptors, and cloned human 5-HT(1A) receptors, in comparison to prazosin, (+)-cyclazosin, 1 and BMY 7383. It turned out that the cystamine- bearing quinazoline 3 (cystazosin) has a reversed affinity profile relative to (+)-cyclazosin owing to a higher affinity for α(1D)-adrenoceptors and a significantly lower affinity for the α(1A) and α(1B) subtypes. Furthermore, in comparison to BMY 7378, cystazosin (3) displays a much better specificity profile since it has lower affinity for D2 and 5-HT(1A) receptors.

Minarini A., Budriesi R., Chiarini A., Leonardi A., Melchiorre C. (1998). Search for α1-adrenoceptor subtypes selective antagonists: Design, synthesis and biological activity of cystazosin, an α(1D)-adrenoceptor antagonist. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 8(11), 1353-1358 [10.1016/S0960-894X(98)00217-0].

Search for α1-adrenoceptor subtypes selective antagonists: Design, synthesis and biological activity of cystazosin, an α(1D)-adrenoceptor antagonist

Minarini A.;Budriesi R.;Chiarini A.;Melchiorre C.
1998

Abstract

Two novel quinazolines (2 and 3) related to both prazosin and its open analogue 1 were synthesized, and their biological profile at α1- adrenoceptor subtypes was assessed by functional assays in rat isolated tissues, namely prostatic vas deferens (α(1A)), spleen (α(1B)) and aorta (α(1D)). Furthermore, the binding profile of 3 was assessed at native α2 and D2 receptors, and cloned human 5-HT(1A) receptors, in comparison to prazosin, (+)-cyclazosin, 1 and BMY 7383. It turned out that the cystamine- bearing quinazoline 3 (cystazosin) has a reversed affinity profile relative to (+)-cyclazosin owing to a higher affinity for α(1D)-adrenoceptors and a significantly lower affinity for the α(1A) and α(1B) subtypes. Furthermore, in comparison to BMY 7378, cystazosin (3) displays a much better specificity profile since it has lower affinity for D2 and 5-HT(1A) receptors.
1998
Minarini A., Budriesi R., Chiarini A., Leonardi A., Melchiorre C. (1998). Search for α1-adrenoceptor subtypes selective antagonists: Design, synthesis and biological activity of cystazosin, an α(1D)-adrenoceptor antagonist. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 8(11), 1353-1358 [10.1016/S0960-894X(98)00217-0].
Minarini A.; Budriesi R.; Chiarini A.; Leonardi A.; Melchiorre C.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/911733
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